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Abstract Organic contaminants have increasingly become a main threat to the water environment, necessitating novel methods for removing from polluted water. In this study, a kind of magnetic ethyl acetate microdrops (Fe3O4@KCC-1@EA) is fabricated for this purpose The KCC-1 shell of Fe3O4@KCC-1 nanospheres is a layer of silica with a dendritic fibrous structure. The ethyl acetate shell of the Fe3O4@KCC-1@EA microdrops provides them with the properties of an organic solvent. While the magnetic core makes them magnetically manipulable. Adding Fe3O4@KCC-1@EA microdrops to bisphenol A-polluted water allows the contaminants to be extracted into the ethyl acetate shell. These microdrops, saturated with bisphenol A, are then easily separated from the water phase with an external magnetic field, achieving a removal rate of over 98%. Besides bisphenol A, the Fe3O4@KCC-1@EA microdrops could also be employed to remove other organic contaminants. This method could provide a new pathway for water purification from organic contaminants.

Abstract Background The purpose of the present study was to evaluate the efficacy and safety of da Vinci robot-assisted thoracoscopic surgery (RATS) versus video-assisted thoracoscopic surgery (VATS) for the treatment of patients with mediastinal tumors of different body mass indices (BMI). Methods A retrospective cohort study was used to collect 260 patients with mediastinal tumors admitted to three medical centers in China from December 2020 to March 2024. These patients underwent mediastinal tumor resection by RATS (n = 125) or VATS (n = 135). Propensity score matching (PSM) analysis was performed for the both groups, and further, the patients were divided into the N-BMI group (18.5 kg/m2 ≤ BMI

Objective To retrospectively analyze the blood transfusion of 322 patients with Stanford type A aortic coarctation in our hospital, and to explore the influencing factors of perioperative blood transfusion in patients and evaluate the effect. Methods The patients with Stanford A type aortic coarctation who underwent surgical treatment in our hospital from October 2020 to October 2023 were selected to analyze the differences in blood transfusion and the monitoring of blood routine and coagulation function between different surgical modalities, and to evaluate the influencing factors of massive blood transfusion. Results The intraoperative allogeneic red blood cell transfusion rate was 63.98% and the perioperative allogeneic red blood cell transfusion rate was 85.71% in patients with Stanford type A aortic coarctation. The intraoperative red blood cell, plasma, cryoprecipitates and platelet transfusion volumes for the Bentall procedure were (3.75±3.81) U, (608.13±314.77) mL, (15.25±8.39) U and (1.53±0.78) therapeutic doses, respectively, and had no difference compared with those for Sun′s procedure with the transfusion volume of (3.13±4.04) U, (707.61± 461.21) mL, (15.79±6.59) U and (1.54±0.64) therapeutic doses and those for Bentall&Sun’s procedure with the transfusion volume of (3.04±4.41) U, (813.48±582.02) mL, (18.39±6.43) U and (1.76±0.58) therapeutic doses(P>0.05). Preoperative hemoglobin levels were significantly lower in patients treated with Bentall procedure (127.75±23.17) g/L and in patients treated with Sun′s procedure (126.07±16.14) g/L than in patients treated with Bentall & Sun′s procedure(133.17±18.12) g/L(P0.05). Perioperative erythrocyte massive infusion accounted for 53.42%. The length of hospital days(days) in the massive transfusion group (23.83±9.74) was significantly higher than that in the conventional transfusion group (31.71±22.98), and the mortality rate in the massive infusion group 34.88% was significantly higher than that in the conventional transfusion group (5.33%)(P

Abstract New coupling scheme substrate‐integrated waveguide (SIW) diplexers based on dual‐mode cavities are proposed for millimetre‐wave applications. Dual‐mode SIW cavities are simultaneously employed in common input and coupling cavity to produce filtering transmission poles and transmission zero (TZ). A common input SIW cavity with two orthogonal modes is employed instead of the traditional T‐junction for circuit miniaturisation, insertion‐loss reduction, and intrinsically high isolation. A critical dual‐mode SIW cavity with diagonally distributed modes has been employed in each channel to realise a controllable stopband TZ for high selectivity of passband's skirt. To further improve channel isolation and passbands' selectivity, a SIW diplexer based on dual‐ and single‐mode cavities is proposed, and four‐pole responses for each passband channel are designed. For the verification, two millimetre‐wave diplexers have been fabricated and tested.

Abstract Background There is a paucity of data regarding sex-oriented analyses of connection between muscle quantity and quality and health-related quality of life (HRQoL), taking into account the pathophysiological differences of sarcopenia/myosteatosis in males versus females. We sought to investigate the associations between skeletal muscle index (SMI)-defined sarcopenia and intramuscular adipose tissue content (IMAC)-defined myosteatosis and EuroQol-5D (EQ-5D)-defined HRQoL in patients with decompensated cirrhosis concerning sex disparities. Methods Totally, 382 patients were enrolled. The relationship between SMI/IMAC and HRQoL was evaluated with restricted cubic spline and Pearson correlation analyses. Furthermore, association between SMI or sarcopenia and EQ-5D utility index was determined by multiple linear regression, adjusted for age, BMI and concurrent disease severity. Results The study population comprised evenly distributed male and female patients (190: 192), mean age 61.9 years. The prevalence of sarcopenia (40.5 versus 9.9%, P

Abstract Over the past two decades, mesenchymal stem/stromal cell (MSC) therapy has made substantial strides, transitioning from experimental clinical applications to commercial products. MSC therapies hold considerable promise for treating refractory and critical conditions such as acute graft-versus-host disease, amyotrophic lateral sclerosis, and acute respiratory distress syndrome. Despite recent successes in clinical and commercial applications, MSC therapy still faces challenges when used as a commercial product. Current detection methods have limitations, leaving the dynamic biodistribution, persistence in injured tissues, and ultimate fate of MSCs in patients unclear. Clarifying the relationship between the pharmacokinetic characteristics of MSCs and their therapeutic effects is crucial for patient stratification and the formulation of precise therapeutic regimens. Moreover, the development of advanced imaging and tracking technologies is essential to address these clinical challenges. This review provides a comprehensive analysis of the kinetic properties, key regulatory molecules, different fates, and detection methods relevant to MSCs and discusses concerns in evaluating MSC druggability from the perspective of integrating pharmacokinetics and efficacy. A better understanding of these challenges could improve MSC clinical efficacy and speed up the introduction of MSC therapy products to the market.

Abstract Mesenchymal stromal/stem cells (MSC) have emerged as a promising therapeutic avenue for treating autoimmune diseases, eliciting considerable interest and discussion regarding their underlying mechanisms. This study revealed the distinctive ability of human umbilical cord MSC to aggregate within the lymph nodes of mice afflicted with autoimmune diseases, but this phenomenon was not observed in healthy mice. The specific distribution is driven by the heightened expression of the CCL21-CCR7 axis in mice with autoimmune diseases, facilitating the targeted homing of MSC to the lymph nodes. Within the lymph nodes, MSC exhibit a remarkable capacity to modulate Th17 cell function, exerting a pronounced anti-inflammatory effect. Transplanted MSC stimulates the secretion of L-amino-acid oxidase (LAAO), a response triggered by elevated levels of tumor necrosis factor-α (TNF-α) in mice with autoimmune diseases through the NF-κB pathway. The presence of LAAO is indispensable for the efficacy of MSC, as it significantly contributes to the inhibition of Th17 cells. Furthermore, LAAO-derived indole-3-pyruvic acid (I3P) serves as a potent suppressor of Th17 cells by activating the aryl hydrocarbon receptor (AHR) pathway. These findings advance our understanding of the global immunomodulatory effects exerted by MSC, providing valuable information for optimizing therapeutic outcomes.

Background: Soil salinization is one of the key factors restricting the production of cropland. Once rice is subjected to alkali stress at the bud burst stage, the yield will suffer irreparable serious loss. Compared with salt tolerance, studies on QTL mapping and candidate gene analysis of rice alkali tolerance are limited. Results: In this study, we used the F2:3 population derived from the alkali-tolerant cultivar LD21 and the alkali-sensitive cultivar WL138 to construct an alkali-tolerant DNA mixing pool, and the BSA (Bulked Segregation Analysis) method was used for re-sequencing. The main QTL qRSLB9 controlling the relative shoot length of rice under alkali stress was mapped by QTL-seq. The candidate interval was narrowed to 346.5 kb by regional linkage mapping, which containing 6 DEGs screened through transcriptome sequencing. The qRT-PCR and candidate gene sequencing showed that LOC_Os09g24260 was most likely to control relative shoot length (RSL) in rice as a major gene who encodes the WD domain, G-beta repeat domain-containing protein. Conclusions: Based on these results, LOC_Os09g24260 was the candidate gene of qRSLB9 conferring alkalinity tolerance to rice at the bud burst stage. Our study provides valuable genetic information and materials for breeding new rice varieties with alkalinity tolerance.How to cite: Wang J, Bian J, Liu L, et al. Screening and analysis of candidate genes conferring alkalinity tolerance in rice (Oryza sativa L.) at the bud burst stage based on QTL-seq and RNA-seq. Electron J Biotechnol 2024;71. https://doi.org/10.1016/j.ejbt.2024.07.002.

Abstract Oxidative stress and neuroinflammation contribute to schizophrenia (SCZ) pathology and may influence treatment efficacy. Matrix metalloproteinase 9 (MMP9) is a critical molecular node mediating the interaction between oxidative stress and inflammation, and so may influence treatment efficacy. Here we examined the associations of plasma MMP9 concentration with antipsychotic drug responses, clinical symptoms, and brain structure. A total of 129 healthy controls and 124 patients with SCZ were included in this study. Patients were monitored clinically during 8 weeks of antipsychotic treatment and classified as poor responders (n = 49) or good responders (n = 75). We then compared plasma MMP9 concentrations in healthy controls at baseline and both SCZ responder groups at baseline and after the 8-week antipsychotic treatment regimen. Cognitive function was also examined using the MATRICS Consensus Cognitive Battery. In addition, we extracted regional white matter density from magnetic resonance images of patients. Compared to healthy controls, plasma MMP9 levels were significantly elevated in poor responders at baseline and negatively correlated with both white matter density in the right superior temporal gyrus and the change in cognitive symptoms after treatment. Conversely, there was no significant difference in plasma MMP9 between good responders and healthy controls, and no associations of plasma MMP9 with cognitive symptoms or regional white matter density among good responders. Elevated plasma MMP9 is associated with poor antipsychotic drug efficacy and white matter deficits in SCZ patients, and so may be a useful biomarker to guide personalized treatment.

Abstract Background Treatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients. Methods Cancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed. Results Fifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2–186) days and the median duration of tofacitinib treatment was 52.5 (range, 3–277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P

Abstract Immunotherapy confers little to no benefit in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Mechanistic insights suggested that epidermal growth factor receptor (EGFR) antibody plus irinotecan might augment the tumor immune response in mCRC. Therefore, we conducted a proof-of-concept, single-arm, phase 2 study (ChiCTR identifier: ChiCTR2000035642) of a combination treatment regimen including tislelizumab (anti-PD-1), cetuximab (anti-EGFR) and irinotecan in 33 patients with MSS and RAS wild-type (WT) mCRC who were previously treated with ≥2 lines of therapy. The primary endpoint was met, with a confirmed objective response rate of 33%. As secondary endpoints, the disease control rate was 79%, and the median progression-free survival and overall survival were 7.3 and 17.4 months respectively. Among the 33 patients, 32 (97.0%) had treatment-related adverse events (AEs). Three (9.1%) reported grade ≥ 3 AEs, including rash (n = 1), neutropenia (n = 2). The post-hoc evaluation of dynamic circulating tumor DNA using next generation sequencing and the analysis of peripheral immune proteomics landscape using Olink revealed that lower variant allele frequency (VAF) at baseline, greater reduction in VAF on treatment, and a hot peripheral macroenvironment were associated with the treatment response independently. Our study showed the antitumor activity of tislelizumab, cetuximab, and irinotecan combination with a tolerable safety profile in previously treated MSS and RAS WT mCRC.

Abstract Previously, we constructed engineered M. circinelloides strains that can not only utilize cellulose, but also increase the yield of γ-linolenic acid (GLA). In the present study, an in-depth analysis of lipid accumulation by engineered M. circinelloides strains using corn straw was to be explored. When a two-stage temperature control strategy was adopted with adding 1.5% cellulase and 15% inoculum, the engineered strains led to increases in the lipid yield (up to 1.56 g per 100 g dry medium) and GLA yield (up to 274 mg per 100 g dry medium) of 1.8- and 2.3-fold, respectively, compared with the control strain. This study proved the engineered M. circinelloides strains, especially for Mc-C2PD6, possess advantages in using corn straw to produce GLA. This work provided a reference for transformation from agricultural cellulosic waste to functional lipid in one step, which might play a positive role in promoting the sustainable development of biological industry.

Abstract Background Phosphoribosyl pyrophosphate synthetase 2 (PRPS2) is known as an oncogene in many types of cancers, including lung cancer. However, its role in regulating tumor‐associated macrophages (TAM) and myeloid‐derived suppressor cells (MDSC) remains unclear. Our study aimed to explore the involvement of PRPS2 in TAM and MDSC regulation. Methods Stable Lewis lung cancer (LLC) cell lines were established using a lentivirus system. These LLC lines were then used to establish tumor model in mice. The levels of target genes were determined using qPCR, western blotting, and ELISA assays. The percentage of different immune cell types was analyzed using fluorescence‐activated cell sorting. The chemotaxis ability of TAM and MDSC was evaluated using an in vitro transwell chemotaxis assay. Results Notably, PRPS2 was found to regulate the chemotaxis of TAM and MDSC in tumor cells, as evidenced by the positive correlation of PRPS2 expression levels and abundance of TAM and MDSC populations. In addition, the expression of CCL2, mediated by PRPS2, was identified as a key factor in the chemotaxis of TAM and MDSC, as evidenced by a significant reduction in macrophages and MDSC numbers in the presence of the CCL2 antibody. Furthermore, in vivo experiments confirmed the involvement of PRPS2 in mediating CCL2 expression. PRPS2 was also found to regulate immune cell infiltration into tumors, whereas knockdown of CCL2 reversed the phenotype induced by PRPS2 overexpression. In tumor tissues from mice implanted with LLC‐PRPS2‐shCCL2 cells, a notable increase in CD4+ and CD8+ T cell percentages, alongside a marked decrease in TAMs, M‐MDSC, and PMN‐MDSC, was observed. Conclusion Taken together, PRPS2 plays a crucial role in modulating the antitumor immune response by reprogramming CCL2‐mediated TAM and MDSC.

Abstract In sociological research based on online public opinion, scholars often overlook the delay and combinatory nature of online responses to real-world events. This study aims to explore the delayed and combinatory responses of online public opinion to the intensity of the COVID-19 pandemic. Specifically, we seek to answer the following questions: (a) Is there a temporal delay in the response of online public opinion to the intensity of the pandemic? (b) Does this delay exhibit general characteristics of social networks, such as combinatory effects and higher-order interactions? To address these questions, we employ natural language processing techniques to extract online public opinion data and utilize statistical and machine learning-based causal inference methods for analysis. The findings indicate that online public opinion’s response to the intensity of COVID-19 is not immediate but rather exhibits a long-term lag. Identical COVID-19 intensity data can trigger multiple delayed public opinion responses, while a single delayed public opinion datum may be influenced by multiple preceding COVID-19 intensity data points. This delayed response of online public opinion and its higher-order network characteristics result in a waveform structure of real-world impacts influenced by online public opinion. We also utilized machine learning causal inference techniques to investigate the sensitivity differences in online public opinion responses to COVID-19 during various time periods.

Abstract Rheumatoid arthritis (RA) is a common autoimmune disease, and some observational studies have indicated an association between Gastroesophageal Reflux Disease (GERD) and RA. However, the causal relationship between the two remains uncertain. We used Mendelian randomization (MR) to assess the causal relationship between GERD and RA. Two-sample Mendelian randomization analysis was performed using pooled data from large-scale genome-wide association studies. In addition, we performed multivariate MR analyses to exclude confounding factors between GERD and RA, including smoking quantity, drinking frequency, BMI, depression, and education attainment. The MR results for GERD on RA suggested a causal effect of the genetic susceptibility of GERD on RA (discovery dataset, IVW, odds ratio [OR] = 1.41, 95% confidence interval [CI] 1.22–1.63, p = 2.81 × 10−6; validation dataset, IVW, OR = 1.38, 95% CI 1.23–1.55, P = 1.76 × 10−8). Multivariate MR analysis also supports this result. But the results of the reverse MR analysis did not reveal compelling evidence that RA can increase the risk of developing GERD. Our bidirectional Two-Sample Mendelian randomization analysis and multivariate MR analysis provide support for the causal effect of GERD on RA. This discovery could offer new insights for the prevention and treatment of RA.

Abstract Aims/Introduction Our aim was to investigate the optimal fasting glucose (FPG) range in Chinese older adults with type 2 diabetes, and to clarify whether the optimal range varies according to the control of risk factors. Materials and Methods The baseline survey for the cohort study began in 2018, with follow up ending in 2022. Our study enrolled 59,030 older diabetes patients with no history of cardiovascular disease (CVD). Participants were divided into nine groups based on their baseline glycemic status. The association between FPG and the risk of adverse outcomes was mainly estimated by multivariate Cox proportional risk models and restricted spline analysis. Results During the 4‐year follow‐up period, a total of 5,637 deaths and 4,904 CVD events occurred. The associations of FPG with mortality and CVD events showed J‐shaped curves. Among all‐cause deaths, the hazard ratios for FPG ≤4.50 and >11.50 mmol/L were 1.50 (95% confidence interval [CI] 1.31–1.71) and 1.84 (95% CI 1.67–2.02). Among CVD, the hazard ratios for FPG ≤4.50 and >11.50 mmol/L were 1.31 (95% CI 1.13–1.53) and 1.71 (95% CI 1.54–1.89), respectively. The optimal FPG ranges of all‐cause mortality and CVD were 5.50–7.50 and 4.50–7.50 mmol/L, respectively. For participants with at least two risk factors, the optimal FPG levels were higher than those with fewer risk factors. Conclusions In older Chinese diabetes patients, the FPG ranges related to the minimum death and CVD event rates were 5.50–7.50 and 4.50–7.50 mmol/L, respectively. Patients with more cardiovascular risk factors had higher optimal blood glucose ranges than those with fewer risk factors.

Introduction: Emerging severe acute respiratory syndrome (SARS) coronavirus (CoV)-2 causes a global health disaster and pandemic. Seeking effective anti-pan-CoVs drugs benefit critical illness patients of coronavirus disease 2019 (COVID-19) but also may play a role in emerging CoVs of the future. Objectives: This study tested the hypothesis that alisol B 23-acetate could be a viral entry inhibitor and would have proinflammatory inhibition for COVID-19 treatment. Methods: SARS-CoV-2 and its variants infected several cell lines were applied to evaluate the anti-CoVs activities of alisol B 23-aceate in vitro. The effects of alisol B 23-acetate on in vivo models were assessed by using SARS-CoV-2 and its variants challenged hamster and human angiotensin-converting enzyme 2 (ACE2) transgenic mice. The target of alisol B 23-acetate to ACE2 was analyzed using hydrogen/deuterium exchange (HDX) mass spectrometry (MS). Results: Alisol B 23-acetate had inhibitory effects on different species of coronavirus. By using HDX-MS, we found that alisol B 23-acetate had inhibition potency toward ACE2. In vivo experiments showed that alisol B 23-acetate treatment remarkably decreased viral copy, reduced CD4+ T lymphocytes and CD11b+ macrophages infiltration and ameliorated lung damages in the hamster model. In Omicron variant infected human ACE2 transgenic mice, alisol B 23-acetate effectively alleviated viral load in nasal turbinate and reduced proinflammatory cytokines interleukin 17 (IL17) and interferon γ (IFNγ) in peripheral blood. The prophylactic treatment of alisol B 23-acetate by intranasal administration significantly attenuated Omicron viral load in the hamster lung tissues. Moreover, alisol B 23-acetate treatment remarkably inhibited proinflammatory responses through mitigating the secretions of IFNγ and IL17 in the cultured human and mice lymphocytes in vitro. Conclusion: Alisol B 23-acetate could be a promising therapeutic agent for COVID-19 treatment and its underlying mechanisms might be attributed to viral entry inhibition and anti-inflammatory activities.

Abstract Introduction We aimed to describe the risk profile of respiratory syncytial virus (RSV) infections among adults ≥ 60 years in Valladolid from January 2010 to August 2022, and to compare them with influenza and COVID-19 controls. Methods This was a retrospective cohort study of all laboratory-confirmed RSV infections identified in centralized microbiology database during a 12-year period. We analyzed risk factors for RSV hospitalization and severity (length of stay, intensive care unit admission, in-hospital death or readmission

To solve the problem of low removal rate and poor N2 selectivity in direct electrochemical ammonia oxidation (EAO), commercial Ni foam and Cu foam were used as anode and cathode of the EAO system, respectively. The coupling effect between the cathode and anode promoted nitrogen cycling during the reaction process, which improved N2 selectivity of the reaction system and promoted it to achieve a high ammonia removal rate. This study showed that the thin Ni(OH)2 with oxygen vacancy formed on the surface of Ni foam anode played an effective role in the dimerization of intermediate products in ammonia oxidation to form N2. This electrochemical system was used to treat real goose wastewater containing 422.5 mg/L NH4+-N and 94.5 mg/L total organic carbon (TOC). After treatment, this electrochemical system achieved good performance with an ammonia removal rate of 87%, N2 selectivity of 77%, and TOC removal rate of 72%. Therefore, this simple and efficient system with Ni foam anode and Cu foam cathode is a promising method for treating ammonia nitrogen wastewater. HIGHLIGHTS The use of commercial electrodes has increased the practicality of this system.; The anode was responsible for the ammonia oxidation.; The cathode was responsible for the reduction of nitrate.; The nitrogen cycle between the electrodes enabled this system to achieve high performance.; The electrochemical system had achieved significant results in practical goose wastewater treatment.;

BACKGROUND AND OBJECTIVES: Current treatment strategies for elderly patients with acute lower limb ischemia (ALLI) have no definitive effect, and studies have reported no definitive prognostic factors that reflect poor outcomes among patients with ALLI. Therefore, reliable clinical indicators that can accurately predict outcomes and guide the choice of treatment options are needed. This study aimed to identify prognostic factors among the elderly patients who underwent endovascular treatment for ALLI. DESIGN: Retrospective. MATERIALS AND METHODS: From January 2011 to December 2020, 270 patients (281 limbs; 124 males; mean age: 84.8 years [range, 80–102 years]) underwent endovascular therapy for ALLI, including acute limb arterial embolism (191 limbs) and acute exacerbation of chronic ischemia (90 limbs). Factors identified through univariate analysis (P < 0.1) and other variables considered likely to have important prognostic value were tested in a logistic regression model for symptom improvement, major amputation, and all-cause mortality. RESULTS: The mean age of the patients was 84.8 years, 54.1% were female, and hypertension (69.0%) was the most common coexisting disease. Patients in the acute group exhibited higher rates of atrial fibrillation (45.5% vs. 24.4%; P = 0.001) and chronic renal failure (15.2% vs. 6.7%; P = 0.044) than the acute-on-chronic group. The acute group exhibited significantly higher plasma D-dimer levels than the acute-on-chronic group (1.59 vs. 1.06; P < 0.001). In the acute group, 145 (75.9%) limbs had preacute Rutherford Classification (RC) of Grade I. In the acute-on-chronic group, 47 (52.2%) limbs had symptom duration of 7–14 days, and 84 (93.3%) limbs were diagnosed with arteriosclerosis obliterans. Most patients opted for antiplatelet therapy, particularly those in the acute-on-chronic group. Multivariate logistic regression analysis revealed that onset time, hypertension, white blood cell (WBC) count, and lesion nature were independent factors for postoperative symptom improvement, whereas hypertension, WBC count, and preacute RC grade were independent factors for amputation at 3 months postoperatively. CONCLUSIONS: WBC count was a major risk factor for postoperative symptom improvement and amputation within 3 months among elderly patients; the higher the WBC count, the higher the risk for amputation. In addition, among patients >80 years of age, early surgery could significantly improve the prognosis of ALLI, regardless of the procedure used to restore blood supply.

Abstract Molecular pathways mediating systemic inflammation entering the brain parenchyma to induce sepsis-associated encephalopathy (SAE) remain elusive. Here, we report that in mice during the first 6 hours of peripheral lipopolysaccharide (LPS)-evoked systemic inflammation (6 hpi), the plasma level of adenosine quickly increased and enhanced the tone of central extracellular adenosine which then provoked neuroinflammation by triggering early astrocyte reactivity. Specific ablation of astrocytic Gi protein-coupled A1 adenosine receptors (A1ARs) prevented this early reactivity and reduced the levels of inflammatory factors (e.g., CCL2, CCL5, and CXCL1) in astrocytes, thereby alleviating microglial reaction, ameliorating blood-brain barrier disruption, peripheral immune cell infiltration, neuronal dysfunction, and depression-like behaviour in the mice. Chemogenetic stimulation of Gi signaling in A1AR-deficent astrocytes at 2 and 4 hpi of LPS injection could restore neuroinflammation and depression-like behaviour, highlighting astrocytes rather than microglia as early drivers of neuroinflammation. Our results identify early astrocyte reactivity towards peripheral and central levels of adenosine as an important pathway driving SAE and highlight the potential of targeting A1ARs for therapeutic intervention.

Abstract Social media-based investor sentiment proxies provide a brand new solution to recognize and measure investor sentiment. Aggregating individual social media text sentiments into public sentiments through a specific aggregation method is a necessary part of constructing an investor sentiment index for social media. The choice or design of the aggregation method directly affects whether or not the researcher can capture the sentiment of the market. This study provides the first systematic review of mainstream methods for aggregating investor sentiment from social media. In addition, we systematically discuss some of the key issues of historical researchers in aggregating investor sentiment, such as neutral sentiment text, simple aggregation of directly aggregated text, etc. The findings suggest that the aggregation method used by researchers directly affects the reliability of investor sentiment indices. Therefore, scholars should carefully choose sentiment aggregation algorithms based on the combination of datasets and sentiment tracking tools and articulate their rationale. This study provides important references for behavioral finance, social media mining, and microinvestor sentiment metrics.

Abstract Background Crohn’s disease (CD) patients require varying levels of supportive care. In order to facilitate caregivers and nurses in precisely evaluating the caregiving requirements of these patients, we developed the CD-specific Care Needs Scale (CD-CNS). Methods This study employed a mixed-methods approach, integrating qualitative and quantitative methodologies. The initial items of the scale were developed through qualitative interviews, Delphi expert consultation, and literature review, while the final items were refined through clinical testing. Qualitative interviews were conducted based on the supportive care needs framework and Maslow’s hierarchy of needs, and scale items were constructed through a literature search and qualitative interviews. The initial version of the scale with 45 items was obtained after the items were verified and modified by expert consultation. A total of 250 CD patients admitted to the gastroenterology department of a hospital in China were selected for verification of the initial version of the scale. A self-designed general questionnaire was used to obtain patients’ medical history and sociodemographic data, and the Chinese version of the Inflammatory Bowel Disease Questionnaire (IBDQ) was used as the criterion. Exploratory factor analysis (EFA) was performed on the CD-CNS to evaluate the dimensions, factor structure, reliability, criterion validity, and construct validity. Results EFA identified 5 dimensions and retained 27 items with strong internal consistency reliability (α = 0.940). The Cronbach’s α coefficients for each dimension ranged from 0.824 to 0.921. Criterion validity was assessed using Spearman’s coefficient, which demonstrated a significant correlation with the IBDQ (P

Abstract Background The function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals. Results Bacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca2+, Mg2+, and Zn2+, and we found that depletion of these ions blocked the hydrolysis of ATP and the formation of adenosine in human blood, resulting in ATP accumulation and dysregulation of PMN functions equivalent to those observed in response to aging. Conclusions Our findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at restoring plasma ATPase activity may offer novel therapeutic opportunities to reduce immune dysfunction, inflammation, and infectious complications in older patients.

Abstract Background Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Method First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. Results The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978–0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. Conclusion These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

Objective To investigate the efficacy and safety of a Compound Acid in improving seborrheic dermatitis of the scalp. Methods Fifty patients with seborrheic dermatitis who met the inclusion criteria were enrolled. The subjects underwent scalp brushing with Compound Acid for a total of four brushings, with the first acid brushing on the day of enrollment and subsequent brushings at one-week interval. Symptom scores were assessed before each acid brushing. A follow-up examination was conducted two weeks after the last acid brushing. Clinical signs and symptoms such as papules, greasiness, erythema, and dandruff were scored using skin microscopy. The status of Malassezia infection was detected using fungus fluorescent microscope. A questionnaire was used to evaluate subjects' scalp itching and pain. Results Forty-seven subjects completed this study. Following the use of the Compound Acid, subjects showed significant improvements in maculopapule scores (from 2.09±1.25 to 0.13±0.34), greasiness scores (from 3.19±0.77 to 0.87±0.65), erythema scores (from 3.23±0.63 to 0.43±0.68), and dandruff scores (from 3.26±0.94 to 0.55±0.65) (all P

Background and objective Lung cancer is the cancer with the highest incidence and mortality rates in China, and non-small cell lung cancer (NSCLC) accounts for 80%-85% of all malignant lung tumors. Currently, surgical treatment remains the primary treatment modality for lung cancer. In recent years, the effectiveness of immune checkpoint inhibitors for NSCLC has become a consensus, and neoadjuvant immunochemotherapy (nICT) has shown promising efficacy and safety in early to intermediate stage NSCLC. However, there are fewer studies related to nICT for locally advanced NSCLC. This study aims to evaluate the efficacy and safety of nICT therapy in locally advanced resectable NSCLC. Methods 85 confirmed resectable stage IIIA and IIIB patients treated in the Department of Thoracic Surgery, Second Hospital of Lanzhou University, from January 2021 to April 2024, were divided into the nICT group (n=32) and the surgery alone group (n=53). Clinical baseline data, perioperative indicators, postoperative complications, imaging response rate, pathological response rate, incidence of adverse events, and quality of life were compared between the two groups. Results There were no statistically significant differences in clinical baseline data between the two groups (P>0.05). Incidence of choosing thoracotomy was higher in the nICT group than in the surgery alone group (P=0.002). There were no significant differences in surgical time, intraoperative blood loss, number of dissected lymph nodes, duration of chest tube placement, postoperative hospital stay, and R0 resection rate between the two groups (P>0.05). The overall incidence of postoperative complications was 31.25% in the nICT group and 22.64% in the surgery alone group, with no statistically significant difference (P=0.380). In the nICT group, the objective response rate (ORR) was 84.38%, with 5 cases of complete response (CR)(15.63%), 22 cases of partial response (PR)(68.75%), 15 cases of pathological response rate (pCR)(46.88%), and 11 cases of major pathological reaponse (MPR) (34.38%). During nICT treatment, 12 cases (37.50%) experienced grade 3 treatment-related adverse events, no death induced by adverse events or immune related adverse events. Moreover, the symptoms of the patients were improved after nICT treatment. Conclusion Neoadjuvant immunochemotherapy shows promising efficacy in locally advanced resectable NSCLC, with manageable treatment-related adverse events. It is a safe and feasible neoadjuvant treatment modality for locally advanced resectable NSCLC.

Abstract Borocarbonitride (BCN) materials have shown significant potential as photocatalysts for hydrogen production. However, traditional bulk BCN exhibits only moderate photocatalytic activity. In this study, we introduce an environmentally conscious and sustainable strategy utilizing biomass-derived carbon sources to synthesize BCN nanosheets. The hydrogen evolution efficiency of BCN-A nanosheets (110 μmol h−1 g−1) exceeds that of bulk BCN photocatalysts (12 μmol h−1 g−1) by 9.1 times, mainly due to the increased surface area (205 m2g−1) and the presence of numerous active sites with enhanced charge separation capabilities. Notably, the biomass-derived BCN nanosheets offer key advantages such as sustainability, cost-effectiveness, and reduced carbon footprint during hydrogen production. These findings highlight the potential of biomass-based BCN nanomaterials to facilitate a greener and more efficient route to hydrogen energy, contributing to the global transition towards renewable energy solutions.

Abstract Aim Clinical diagnosis and surgical treatment of chondrosarcoma (CS) are continuously improving. The purpose of our study is to evaluate the effectiveness of microwave ablation (MWA) assisted degradation therapy in the surgical treatment of intramedullary chondrosarcoma of the extremities, to provide a new reference and research basis for the surgical treatment of CS. Methods We recruited 36 patients with intramedullary CS who underwent MWA assisted extended curettage. Preoperative patient demographics and clinical data were recorded. Surgery was independently assisted by a medical team. Patients were followed up strictly and evaluated for oncological prognosis, radiological results, limb joint function, pain, and complications. Results We included 15 men and 21 women (mean age: 43.5 ± 10.1). The average length of the lesion was 8.1 ± 2.5 cm. Based on preoperative radiographic, clinical manifestations, and pathological results of puncture biopsy, 28 patients were preliminarily diagnosed with CS-grade I and eight patients with CS-grade II. No recurrence or metastasis occurred in the postoperative follow-up. The average Musculoskeletal Tumor Society score was 28.8 ± 1.0, significantly better than presurgery. Secondary shoulder periarthritis and abduction dysfunction occurred in early postoperative stage CS of the proximal humerus in some, but returned to normal after rehabilitation exercise. Secondary bursitis occurred at the knee joint in some due to the internal fixation device used in treatment; however, secondary osteoarthritis and avascular necrosis of the femoral head were not observed. Overall, oncological and functional prognoses were satisfactory. Conclusions The application of MWA assisted degradation therapy in intramedullary CS can achieve satisfactory oncology and functional prognosis, providing a new option for the limited treatment of CS.

In a genome-wide association study, we identified a rice UDP-glycosyltransferase gene, OsUGT706D2, whose transcription was activated in response to cold and submergence stress and to exogenous abscisic acid (ABA). OsUGT706D2 positively regulated the biosynthesis of tricin-4′-O-(syringyl alcohol) ether-7-O-glucoside at both the transcriptional and metabolic levels. OsUGT706D2 mediated cold and submergence tolerance by modulating the expression of stress-responsive genes as well as the abscisic acid (ABA) signaling pathway. Gain of function of OsUGT706D2 increased cold and submergence tolerance and loss of function of OsUGT706D2 reduced cold tolerance. ABA positively regulated OsUGT706D2-mediated cold tolerance but reduced submergence tolerance. These findings suggest the potential use of OsUGT706D2 for improving abiotic stress tolerance in rice.

Abstract Research based on investor sentiment in social media has been a hot topic of research in behavioral finance, and the reliability of investor sentiment mined from social media is a potential condition for the reliability of the results of these studies. In the past, scholars have often focused on using more reliable tools to track investor sentiment in order to get more reliable investor sentiment. However, less attention has been paid to another key factor affecting the reliability of investor sentiment on social media: the selection and collection of data. In this study, we systematically investigate the process of data selection and collection in relation to the construction of investor sentiment on social media. Our findings suggest that the process of creating a dataset from social media is a process that starts and ends with a research question. In this process, we need to overcome various obstacles to end up with an imperfect dataset. The researchers must take a series of steps to get close to the best dataset and acknowledge some of the shortcomings and limitations. We emphasize that the absence of accepted, reliable standards makes it particularly important to follow basic principles. This study is an important reference for social media-based behavioral finance research.

Abstract Gypsification is a common problem in weathered calcareous relics. In previous studies, the solutions of barium hydroxide in water and methanol were used as protectants for gypsification calcareous relics and showed significant differences in permeability. In this study, the underlying reasons for permeability differences between these two solutions were investigated using optical microscopy, ultraviolet–visible spectrophotometry, X-ray diffractometry, Fourier transform infrared spectroscopy, the phenolphthalein test and physical property characterizations. The results indicated that the permeability differences were primarily caused by the solutions’ reactivity. Specifically, owing to the high reactivity of barium hydroxide in water, it reacted rapidly with atmospheric CO2 and gypsum (the weathering product) to generate barium carbonate, barium sulfate and calcium hydroxide precipitates. These precipitates hindered the penetration of solution into weathered relics. In contrast, barium hydroxide in methanol did not react with atmospheric CO2 or weathered relics, which also kept the solution in a liquid state during the infiltration process. Therefore, the solution of barium hydroxide in methanol exhibited high permeability. Based on the above findings, this study is meaningful for applying barium protectants in the conservation of gypsification calcareous relics.

Objective To investigate the binding and carrying effects of human serum albumin (HSA) from various sources on sphingosine-1-phosphate (S1P). Methods Utilizing human plasma-derived HSA (pHSA) and recombinant HSA (rHSA) samples as the focal points of our investigation, LC-MS/MS technology was employed to meticulously compare and analyze the disparities in S1P content among the aforementioned samples. Subsequently, under physiological concentration conditions, S1P was directly introduced to HSA samples for loading processing, facilitating a comprehensive comparison of the binding efficacy of HSA from different sources to S1P. Within a serum-free culture setting, HSA samples from various sources were co-cultured with HUVEC cells. The alterations in S1P content within the cell culture supernatant across different treatment groups were meticulously analyzed, allowing for a nuanced comparison of the S1P carry effects exerted by HSA from different sources on cells.The interaction between HSA and S1P molecules from different sources was analyzed and their affinity was calculated using surface plasmon resonance (SPR) technology. Furthermore, leveraging AutoDock Vina software and the Molprophet platform, the molecular docking analysis of HSA and S1P was conducted, aiming to predict the key binding pocket domain of S1P within HSA. Results All pHSA samples exhibited detectable levels of S1P (ranging from 3.31±0.03 to 30.35±0.07 μg/L), with significant variations observed among pHSA samples from different manufacturers (P

The evolution of constituent particles and the precipitation behavior in a commercial 2024 alloy during various homogenization regimes and their effect on T4-state mechanical performance have been investigated quantitatively. A typical phase transformation of AlCuFeMn → Al7Cu2Fe + Al20Cu2Mn3 gradually occurred during homogenization was identified as the duration time increasing, resulting in a “composite-particle” configuration with flocculent morphology. Meanwhile, nano-sized T-Al20Cu2Mn3 continuously precipitate within the matrix as the homogenization proceeding. The H1 treatment (445 °C/18 h + 495 °C/2 h) produced the higher number density of T phase with a finer size, while H2 regime (445 °C/18 h + 495 °C/6 h) caused a more complete precipitation and thus increased the fraction of S-texture component after subsequent rolling and T4-treatment. At T4 state, the superior mechanical properties of the H1 plate were obtained compared with the H2 sample, owing to the better dispersion-strengthening effect from T phase. In addition, the higher ductility can be attributed to the less weak-bonding interfaces and less recrystallization resistance from inadequate AlCuFeMn phase transition and T-precipitation, respectively. This work will provide useful insights to regulate the homogenization regimes for 2024 alloys in industrial applications.

Abstract Chimeric antigen receptor T (CAR-T) cells have been proposed for HIV-1 treatment but have not yet demonstrated desirable therapeutic efficacy. Here, we report newly developed anti-HIV-1 CAR-T cells armed with endogenic broadly neutralizing antibodies (bNAbs) and the follicle-homing receptor CXCR5, termed M10 cells. M10 cells were designed to exercise three-fold biological functions, including broad cytotoxic effects on HIV-infected cells, neutralization of cell-free viruses produced after latency reversal, and B-cell follicle homing. After demonstrating the three-fold biological activities, M10 cells were administered to treat 18 HIV-1 patients via a regimen of two allogenic M10 cell infusions with an interval of 30 days, with each M10 cell infusion followed by two chidamide stimulations for HIV-1 reservoir activation. Consequently, 74.3% of M10 cell infusions resulted in significant suppression of viral rebound, with viral loads declining by an average of 67.1%, and 10 patients showed persistently reduced cell-associated HIV-1 RNA levels (average decrease of 1.15 log10) over the 150-day observation period. M10 cells were also found to impose selective pressure on the latent viral reservoir. No significant treatment-related adverse effects were observed. Overall, our study supported the potential of M10 CAR-T cells as a novel, safe, and effective therapeutic option for the functional cure of HIV-1/AIDS.

Abstract Matrix metalloproteinases (MMPs) had a variety of subtypes, which may be related to tumor invasion and angiogenesis, and the polymorphisms from MMPs have been also associated with the susceptibility to a variety of tumors, including prostate cancer (PCa). However, previous studies have not systematically analyzed the association between MMP and prostate cancer, so we conducted systematic data collection and analyzed to evaluate the relationship among polymorphisms in MMPs and PCa susceptibility. We searched PubMed, Web of Science, Embase and Google Scholar for all papers published up to Apr 3rd, 2023, and systematically analyzed the relationship among MMP1-1607 2G/1G, MMP2-1306 T/C, MMP2-735 T/C, MMP7-181 G/A, MMP9-1562 T/C and PCa susceptibility using multiple comparative models and subgroup analyses. We found that MMP2-1306 T/C polymorphism showed associations with PCa susceptibility, with the Ethnicity subgroup (Asian) being more pronounced. Similarly, MMP9-1562 T/C has also had associations with PCa susceptibility. Our current study found that the polymorphisms of, MMP2-1306 T/C, and MMP9-1562 T/C had strong associations with PCa risk.

Abstract Plant metabolites including anthocyanins play an important role in the growth of plants, as well as in regulating biotic and abiotic stress responses to the environment. Here we report comprehensive profiling of 3315 metabolites and a further metabolic-based genome-wide association study (mGWAS) based on 292,485 SNPs obtained from 311 rice accessions, including 160 wild and 151 cultivars. We identified hundreds of common variants affecting a large number of secondary metabolites with large effects at high throughput. Finally, we identified a novel gene namely OsLSC6 (Oryza sativa leaf sheath color 6), which encoded a UDP 3-O-glucosyltransferase and involved in the anthocyanin biosynthesis of Cyanidin-3-Galc (sd1825) responsible for leaf sheath color, and resulted in significant different accumulation of sd1825 between wild (purple) and cultivars (green). The results of knockout transgenic experiments showed that OsLSC6 regulated the biosynthesis and accumulation of sd1825, controlled the purple leaf sheath. Our further research revealed that OsLSC6 also confers resistance to cold stress during the seedling stage in rice. And we identified that a SNP in OsLSC6 was responsible for the leaf sheath color and chilling tolerance, supporting the importance of OsLSC6 in plant adaption. Our study could not only demonstrate that OsLSC6 is a vital regulator during anthocyanin biosynthesis and abiotic stress responses, but also provide a powerful complementary tool based on metabolites-to-genes analysis by mGWAS for functional gene identification andpromising candidate in future rice breeding and improvement.

In this work, hydrogen charged Zircaloy-4 has been investigated under an in-situ electron backscatter diffraction during tensile loading. Aim were, first, to distinguish the hydride phase type and its spatial distribution, second to determine hydride phase transformation (HPT) and orientation relationship (OR) subjected to uniaxial tensile condition, and third to correlate the hydrides evolution and their effect on the micromechanical behavior, such as slip mode activation and lattice rotation, of Zircaloy-4. Apart from the applied stress, the analysis reveals that hydride reorientation is strongly related to temperature and loading mode. We noted that deformation induced δ-ZrH1.5 transformed to γ-ZrH and ε-ZrH2, and the former follows the confirmed OR {0001}α//{111}δ/γ with α//δ/γ, while the latter's OR changed to {10 1‾ 0}α//{121}ε with α//ε after HPT. The coexistence of δ-ZrH1.5 and γ-ZrH or ε-ZrH2 is observed, and the main corresponding OR is {111}δ//{111}γ with δ//γ, and {100}δ//{110}ε with δ//ε, respectively. The characterized microstructure and the measured lattice rotation results indicate that HPT delayed cracking in hydride and promoted deformation in parent grains. As the strain increases, the maintenance of hydride-matrix (H-M) coherent interfaces restricts further lattice rotation. HPT accelerates the hydride decomposition ascribed to the intensification of hydrogen diffusion under stress, and the hydride and the H-M interfaces act as priority sites for initiating microcracks. The sequence of HPT depends on the possibility of activated slip mode among grains. These findings contribute to developing the understanding of the HPT and hydrogen embrittlement.

Abstract Background Quercetin is a flavonol compound widely distributed in plants that possesses diverse biological properties, including antioxidative, anti-inflammatory, anticancer, neuroprotective and senescent cell-clearing activities. It has been shown to effectively alleviate neurodegenerative diseases and enhance cognitive functions in various models. The immune system has been implicated in the regulation of brain function and cognitive abilities. However, it remains unclear whether quercetin enhances cognitive functions by interacting with the immune system. Results In this study, middle-aged female mice were administered quercetin via tail vein injection. Quercetin increased the proportion of NK cells, without affecting T or B cells, and improved cognitive performance. Depletion of NK cells significantly reduces cognitive ability in mice. RNA-seq analysis revealed that quercetin modulated the RNA profile of hippocampal tissues in aging animals towards a more youthful state. In vitro, quercetin significantly inhibited the differentiation of Lin−CD117+ hematopoietic stem cells into NK cells. Furthermore, quercetin promoted the proportion and maturation of NK cells by binding to the MYH9 protein. Conclusions In summary, our findings suggest that quercetin promotes the proportion and maturation of NK cells by binding to the MYH9 protein, thereby improving cognitive performance in middle-aged mice. Graphical abstract

Reactive oxygen species (ROS), immune dysregulation-induced inflammatory outbreaks and microbial imbalance play critical roles in the development of inflammatory bowel disease (IBD). Herein, a novel enzyme-like biomimetic oral-agent ZnPBA@YCW has been developed, using yeast cell wall (YCW) as the outer shell and zinc-doped Prussian blue analogue (ZnPBA) nanozyme inside. When orally administered, the ZnPBA@YCW is able to adhere to Escherichia coli occupying the ecological niche in IBD and subsequently release the ZnPBA nanozyme for removal of E. coli, meanwhile exhibiting improved intestinal epithelial barrier repair. Moreover, it is found that the ZnPBA nanozyme exhibits remarkable capability in restoring redox homeostasis by scavenging ROS and inhibiting NF-κB signaling pathway. More importantly, the 16S ribosomal RNA gene sequencing results indicate that post-oral of ZnPBA@YCW can effectively regulate gut microbiota by enhancing the bacterial richness and diversity, significantly increasing the abundance of probiotics with anti-inflammatory phenotype while downgrading pathogenic E. coli to the same level as normal mice. Such a novel nanomedicine provides a new idea for efficient treating those ROS-mediated diseases accompanying with flora disorders.

IntroductionRhizosphere bacterial community as a valuable indicator of soil quality and function, has been widespread studied. However, little knowledge is about the response of bacterial communities to plant–plant interaction and different fertilizers during secondary forest succession.MethodsWe conducted a field pot experiment applying organic and inorganic fertilizers to monocultures and mixed cultures of dominant plant species from mid- to late-successional stages (Salix oritrepha, Betula albosinensis, and Picea asperata), and investigated the responses of plant growth and rhizosphere bacterial communities.Results and discussionResults indicated that growth rate of plant height varied among plant species, but no significant differences were observed in soil bacterial diversity and composition among plant species or inter-specific interactions under control. Compared to control, inorganic fertilizer resulted in increases in plant growth and the relative abundance of Proteobacteria, Patescibacteria, Bacteroidetes and Gemmatimonadetes, while simultaneously leading to decrease in the relative abundance of Acidobacteria, Actinobacteria, Chloroflexi, Rokubacteria and Planctomycetes. When grown with other species, the bacterial communities in the mixture resembled those of S. oritrepha in singular monoculture under inorganic fertilizer treatment, but plant growth was not affected by interspecific interaction. Unlike inorganic fertilizer, organic fertilizer significantly affected bacterial communities and increased bacterial diversity, but did not alter the effects of plant–plant interactions on bacterial communities. It was also observed that organic fertilizer facilitated later successional species’ growth (P. asperata and B. albosinensis) by the mid-successional species (S. oritrepha), ultimately facilitating secondary forest succession. In addition, plants at different successional stages harbor specific bacterial communities to affect their growth, and the bacterial communities contributed more than soil properties to the variations in the plant growth of S. oritrepha and P. asperata though the bacterial communities were regulated by soil factors. This finding highlights the significance of the rhizosphere bacteria on plant growth and plant community succession. It also emphasize the importance of considering both plant–plant interactions and diverse fertilizer types in forest restoration efforts and provide valuable insights into optimizing agronomic practices for secondary forest succession.

Aedes albopictus, a common mosquito in Zhejiang Province, is a carrier of more than twenty arboviruses. There are dozens or even hundreds of imported cases of dengue fever every year in Zhejiang Province, and there have also been many local outbreaks caused by imported cases of dengue fever. The objectives were to assess the resistance of larvae and adults of several Ae. albopictus strains in Zhejiang Province to commonly used pyrethroid insecticides (beta-cypermethrin, deltamethrin and permethrin), and detect mutations in the sodium channel gene, to further analyse the relationship between phenotypic resistance and the frequency of mutations. The resistance of eight field strains of Ae. albopictus larvae to beta-cypermethrin, deltamethrin and permethrin ranged from 8.17 to 36.06, 12.12–107.3 and 1.55–81.9, respectively, and there was a significant positive correlation of interaction resistance among the three insecticides. The mutation frequencies of I1532T and F1534S in the larvae of Ae. albopictus were 0–6.25 % and 42.19–100.00 %. Moreover, the diagnostic doses of the three pyrethroids for adult Ae. albopictus mosquitoes were 0.2510 g/L, 0.1562 g/L, and 0.9072 g/L. Except for the Zhoushan strain, which was suspected to be resistant to beta-cypermethrin, the other field strains were resistant to the three pyrethroids, and there was a significant positive correlation of cross-resistance among the three insecticides. The mutation frequencies of I1532T and F1534S of adult Ae. albopictus were 0–1.56 % and 62.50–100.00 %. In addition, the LC50 of the larvae and the mortality rate of adult Ae. albopictus after treatment with the three pyrethroids were significantly and positively correlated with the frequency of the F1534S mutation. F1534S mutation occurred earlier than I1532T mutation in both larvae and adult Ae. albopictus. F1534S mutation in the sodium channel gene may be a particular biomolecular detection marker for resistance to pyrethroid insecticides in Ae. albopictus in Zhejiang Province.

Ionic liquid electrolytes (ILEs), distinguished by their nonvolatility and high thermal stability, demonstrate considerable compatibility with silicon anodes and thus are an ideal alternative electrolyte for lithium-ion batteries. However, substantial challenges are to be addressed, notably the poor rate capability predominantly due to excessively tight Li+-coordination in the solvation sheath. Here, we introduce an innovative ILE-based electrolyte tailored for micro-sized silicon (μSi) anodes to address the issue of rate capability. By incorporating nonflammable sulfolane molecules into the primary Li+-solvation sheath, we concurrently enhance de-solvation kinetics and ion-conducting capability of solid electrolyte interphase (SEI). The primary sulfolane-mediated Li+-solvation configuration weakens de-solvation barrier and strengthens inorganic-rich SEI, while impeding the precipitation of organic cations in the SEI formation. The μSi electrode with the sulfolane-mediated ILE delivers an impressive rate capability of 782.5 mA h g–1 at a high current density of 12 A g–1 over 500 cycles Accelerating rate calorimetry further verifies remarkable thermal stability of the derived SEI and superior thermal safety of the sulfolane-mediated ILE compared to the commonly used electrolyte. This work provides an effective way to boost the rate capability of μSi anodes based on ILEs without compromising the thermal safety for developing high-performance lithium-ion batteries.

Abstract Cochlear hair cells are the sensory cells responsible for transduction of acoustic signals. In mammals, damaged hair cells do not regenerate, resulting in permanent hearing loss. Reprogramming of the surrounding supporting cells to functional hair cells represent a novel strategy to hearing restoration. However, cellular processes governing the efficient and functional hair cell reprogramming are not completely understood. Employing the mouse cochlear organoid system, detailed metabolomic characterizations of the expanding and differentiating organoids are performed. It is found that hair cell differentiation is associated with increased mitochondrial electron transport chain (ETC) activity and reactive oxidative species generation. Transcriptome and metabolome analyses indicate reduced expression of oxidoreductases and tricyclic acid (TCA) cycle metabolites. The metabolic decoupling between ETC and TCA cycle limits the availability of the key metabolic cofactors, α‐ketoglutarate (α‐KG) and nicotinamide adenine dinucleotide (NAD+). Reduced expression of NAD+ in cochlear supporting cells by PGC1α deficiency further impairs hair cell reprogramming, while supplementation of α‐KG and NAD+ promotes hair cell reprogramming both in vitro and in vivo. These findings reveal metabolic rewiring as a central cellular process during hair cell differentiation, and highlight the insufficiency of key metabolites as a metabolic barrier for efficient hair cell reprogramming.

Abstract Background The therapeutic advantage of thoracic radiotherapy (tRT) as an adjunct to first‐line immunotherapy and chemotherapy in patients with extensive‐stage small cell lung cancer (ES‐SCLC) remains unclear. We sought to elucidate this in a retrospective cohort study comparing the effectiveness and safety of tRT in combination with first‐line immunotherapy and chemotherapy. Methods Our retrospective study included patients with ES‐SCLC, treated at the West China Hospital between January 2019 and December 2022. They received first‐line immunotherapy and chemotherapy and were categorized into two cohorts based on the administration of tRT. The primary outcomes were overall survival (OS) and progression‐free survival (PFS). Cox regression analysis was utilized to identify potential independent predictors of prognosis and to compare the treatment outcomes across various patient subgroups. Treatment‐related toxicities across both cohorts were compared using the Chi‐squared test. Results A total of 99patients were eligible for the study, out of which 55 received tRT. The medianduration of follow‐up was 39 months. Remarkably, patients who received tRTdemonstrated superior OS and PFS in comparison to those who did not (P

Abstract Despite being one of the most prevalent RNA modifications, the role of N6‐methyladenosine (m6A) in amyotrophic lateral sclerosis (ALS) remains ambiguous. In this investigation, we explore the contribution of genetic defects of m6A‐related genes to ALS pathogenesis. We scrutinized the mutation landscape of m6A genes through a comprehensive analysis of whole‐exome sequencing cohorts, encompassing 508 ALS patients and 1660 population‐matched controls. Our findings reveal a noteworthy enrichment of RNA binding motif protein X‐linked (RBMX) variants among ALS patients, with a significant correlation between pathogenic m6A variants and adverse clinical outcomes. Furthermore, Rbmx knockdown in NSC‐34 cells overexpressing mutant TDP43Q331K results in cell death mediated by an augmented p53 response. Similarly, RBMX knockdown in ALS motor neurons derived from induced pluripotent stem cells (iPSCs) manifests morphological defects and activation of the p53 pathway. Transcriptional analysis using publicly available single‐cell sequencing data from the primary motor cortex indicates that RBMX‐regulated genes selectively influence excitatory neurons and exhibit enrichment in ALS‐implicated pathways. Through integrated analyses, our study underscores the emerging roles played by RBMX in ALS, suggesting a potential nexus between the disease and dysregulated m6A‐mediated mRNA metabolism.

IntroductionAgricultural organic waste recycling can supply nutrients for crop production and partially replace chemical nitrogen fertilizers, which is beneficial for waste management and environmental protection. Nevertheless, comprehensive evaluation of the effects of different organic materials applications on crop yield and the environment is limited.MethodsTherefore, in this study, a comprehensive investigation of the synergistic effects of straw, pig manure, and biogas residue recycling on the wheat (Triticum aestivum L.) and maize (Zea mays L.) systems was carried out in the North China Plain. Field experiments were conducted from 2019 to 2021, comprising five treatments: straw (ST), pig manure (PM), and biogas residue (BR) partially replacing chemical nitrogen fertilizer, sole application of chemical nitrogen fertilizer (CF), and a control with no nitrogen application (WN).Results and discussionThe results showed that organic materials significantly increased soil total nitrogen (3.04%–9.10%) and N recovery efficiency (REN; 42.21%–44.99%), but pig manure was more beneficial in increasing crop yields (3.50%), especially wheat yields (8.72%), and REN was significantly higher than that of the other treatments. Organic materials performed differently in wheat and maize seasons, and wheat yield could be improved by organic materials return. Organic materials stimulated N2O emission in wheat season (4.28%–32.20%), while biogas residue inhibited the N2O emission in maize season (47.47%). The negative effect of straw and biogas residue on yield decreased with increasing years of return, and pig manure continued to contribute to yield. In conclusion, pig manure is the optimal alternative that can increase crop yield, soil N content, and REN without stimulating N2O emissions.

A powder-metallurgy MoNbTaTiV refractory high-entropy alloy synthesized by mechanical alloying (MA) and spark plasma sintering was subjected to hot deformations at different temperatures and strain rates. The microstructural morphologies were characterized, and component element segregation was elucidated. With grain refinement and lattice strain increase, the large inhomogeneous milled powder became refined and homogeneous after the MA. Component element segregation was observed at relatively low deformation temperatures and high strain rates. As the deformation temperature increased and the strain rate decreased, the segregation gradually disappeared, which was attributed to dislocation movement.

A multi-stage planning method for independent energy storage (IES) based on dynamically updating key transmission sections (KTS) is proposed to address issues such as uneven power flow distribution and transmission congestion resulting from the high penetration of renewable energy sources and load growth. First, an IES planning model considering KTS constraints is established by searching and updating the KTS and associated constraints. This model takes into account IES investment and operation costs, maintenance costs, revenue from spot price differences, and penalties for system congestion. Then, a multi-stage planning method for energy storage is proposed based on the dynamic updating of KTS and the annual planning results. To verify the effectiveness and feasibility of the proposed method, a case study simulation is conducted using the improved IEEE 39-bus New England standard system. The results demonstrate the ability of the method to achieve multi-stage rolling optimization of IES, providing a reference for future efforts toward multi-stage planning of IES.

Abstract Background The optimal treatment for esophageal squamous cell carcinoma (ESCC) patients with postoperative recurrence remains controversial. We aimed to evaluate the effects of radiotherapy (RT) and chemoradiotherapy (CRT) on postoperative recurrence in ESCC patients. Methods Recurrence ESCC patients who received salvage RT and CRT from January 2015 to January 2019 were retrospectively reviewed. Post‐recurrence survival (PRS) and prognostic factors were evaluated by Kaplan–Meier and Cox proportional hazards models, respectively. Subgroup analyses were performed based on pathological lymph node (LN) status (negative/positive) to evaluate the differences in salvage treatments and toxic reaction. Results A total of 170 patients were enrolled, with a median age of 60 years (range 43–77). No significant difference was found in the median PRS between the salvage RT and CRT groups (p > 0.05). Multivariate analysis revealed that TNM stage III and IV, macroscopic medullary type, and distant metastasis recurrence pattern were independent prognostic factors (all p